The cellular mechanisms of the action of lithium in the nervous system are of interest because of their importance in treating certain types of mental illness. We tested the effect of lithium on the electrogenic sodium pump and the slow IPSP in bullfrog sympathetic ganglia, using the sucrose gap technique. The administration of acetylcholine (3 mM) produces a nicotinic depolarization followed by an after-hyperpolarization that results from the activation of the electrogenic sodium pump. When sodium in the Ringer's solution was replaced by lithium, the acetylcholine depolarization still occurred but the after-hyperpolarization was abolished. Presumably lithium is not exuded by the electrogenic sodium pump, as has been found previously in other tissues. Lithium Ringer also blocked the muscarinic slow IPSP and the hyperpolarizing response to agonists such as methacholine. We have recently found that ouabain and potassium-free Ringer can effectively inhibit the electrogenic sodium pump without blocking the slow IPSP, indicating that the slow IPSP is not generated by activation of the electrogenic sodium pump. In view of this, we conclude that the effect of lithium on the slow IPSP is not a direct consequence of sodium pump inhibition.